Hydrochloric Acid → HCID 73213874, compound

Participants

Reaction Steps

An ambient temperature suspension of (S)-tert-butyl (1-cyclobutyl-3-((4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)propan-2-yl)carbamate (70 mg, 0.155 mmol) in diethyl ether (1 mL) was treated with HCl (4M in 1,4-dioxane) (0.775 mL, 3.10 mmol) and stirred for 1 h. The resulting mixture was concentrated under reduced pressure to a yellow solid. The crude material was purified by reverse phase high performance liquid chromatography (Phenomenex Luna C18 30×100 mm 10 micron; water/methanol/TFA gradient elution). Fractions containing product were concentrated under reduced pressure. The resulting residue was partitioned between saturated aqueous sodium bicarbonate and ethyl acetate. The layers were separated and the aqueous was extracted twice more with ethyl acetate. The pooled organics were washed once with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure to afford (S)-8-(2-amino-3-cyclobutylpropoxy)-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one (17 mg, 0.046 mmol, 30% yield) as a white solid. LC/MS, (ESI) m/z 352.3 [(M+H)+, calcd for C21H26N3O2 352.2]; HPLC retention time (method C): tR=14.15 min; HPLC retention time (method D): tR=14.78 min; 1H NMR (400 MHz, CHLOROFORM-d) δ 8.64 (d, J=5.8 Hz, 1H), 8.15 (d, J=9.0 Hz, 1H), 7.82 (d, J=5.8 Hz, 1H), 6.89 (dd, J=8.9, 2.4 Hz, 1H), 6.84 (d, J=2.3 Hz, 1H), 4.04 (dd, J=8.9, 3.9 Hz, 1H), 3.86 (dd, J=8.8, 7.5 Hz, 1H), 3.73 (s, 3H), 3.23 (tdd, J=7.5, 5.5, 3.8 Hz, 1H), 3.16 (s, 3H), 2.60-2.43 (m, 1H), 2.21-2.08 (m, 2H), 2.01-1.81 (m, 2H), 1.80-1.55 (m, 4H).

Provenance & Evidence